MassIVE MSV000089863

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Short-Term Modified Atkins Diet Induced Molecular Changes in Epilepsy Brain and Plasma

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Description

Background There is evidence that shifting brain metabolism with high fat and low carbohydrate diets can reduce seizure frequency in some treatment-resistant epilepsy patients, including the more flexible Modified Atkins Diet (MAD) that is more palatable, mimicking fasting and high ketone body levels. Low carbohydrate diets shift brain energy production from glycolysis to fatty acid beta-oxidation, particularly impacting neuron and astrocyte related metabolism. Methods and findings We evaluated the effect of short-term MAD on molecular mechanisms in surgical brain tissue from adult treatment-resistant epilepsy patients and plasma compared to Control participants consuming a non-modified higher carbohydrate diet (failure of > 2 anti-seizure medications; n = 6 MAD, mean age 43.7 years, range 21-53, diet average 10 days; n = 10 Control, mean age 41.9 years, range 28-64). There were 13 altered metabolites in plasma, including increased ketone body 3-hydroxybutyric acid, 1 metabolite in cortex, and 11 metabolites in hippocampus that were associated with mitochondrial function. Cortex and plasma 3-hydroxybutyric acid levels correlated (p = 0.0088, R2 = 0.48). Brain proteomics and RNAseq identified few differences, with trends seen in hippocampal NADH related signaling pathways (activated oxidative phosphorylation and inhibited sirtuin signaling). Conclusions Short-term MAD resulted in early metabolic changes in plasma and resected epilepsy brain tissue, in combination with trending changes seen in hippocampal NADH related signaling pathways. Future studies should evaluate how brain molecular mechanisms are altered with long-term MAD, with correlations to seizure frequency, epilepsy syndrome, and other clinical variables. [Clinicaltrials.gov NCT02565966] [doi:10.25345/C58P5VD7W] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: FFPE ; LFQ proteomics ; Modified Atkins Diet ; Epilepsy

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Principal Investigators:
(in alphabetical order) 		Beatrix Ueberheide, NYU School of Medicine, USA
Submitting User: KanshinED1
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